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Abstract

The purified human immunodeficiency virus type-1 (HIV-1) Tat protein inhibited lymphocyte proliferation induced by tetanus toxoid or Candida antigens by 66 to 97% at nanomolar concentrations of Tat. In contrast, Tat did not cause a significant reduction of lymphocyte proliferation in response to mitogens such as phytohemagglutinin or pokeweed mitogen. Inhibition was blocked by oxidation of the cysteine-rich region of Tat or by incubation with an antibody to Tat before the assay. A synthetic Tat peptide (residues 1 to 58) also inhibited antigen-stimulated proliferation. Experiments with H9 and U937 cell lines showed that Tat can easily enter both lymphocytes and monocytes. The specific inhibition of antigen-induced lymphocyte proliferation by Tat mimics the effect seen with lymphocytes from HIV-infected individuals and suggests that Tat might directly contribute to the immunosuppression associated with HIV infection.

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Science
Volume 246 | Issue 4937
22 December 1989

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Published in print: 22 December 1989

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Raphael P. Viscidi
Eudowood Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Kumudini Mayur
Eudowood Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Howard M. Lederman
Eudowood Division of Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Alan D. Frankel
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.

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